Theragnostic Imaging Using Radiolabeled Antibodies and Tyrosine Kinase Inhibitors

During the past decade, the efficacy of new molecular targeted drugs such as tyrosine kinase inhibitors (TKIs) and monoclonal antibodies has been proven worldwide, and molecular targeted therapies have become the mainstream in cancer therapy. However, clinical use of these new drugs presents unexpected adverse effects or poor therapeutic effects. Therefore, we require diagnostic tools to estimate the target molecule status in cancer tissues and predict therapeutic efficacy and adverse effects. Although immunohistochemical, polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) analyses of biopsy samples are conventional and popular for this diagnostic purpose, molecular imaging modalities such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) are also useful for noninvasive estimation of gene and protein expression and drug pharmacokinetics. In this review, we introduce new radiolabeled TKIs, antibodies, and their clinical application in molecular targeted therapy and discuss the issues of these imaging probes

Mapping of Nematode Resistance in Hexaploid Sweetpotato Using an Next-Generation Sequencing-Based Association Study

The southern root-knot nematode (SRKN; Meloidogyne incognita) is a typical parasitic nematode that affects sweetpotato [Ipomoea batatas (L.) Lam.], causing a significant decrease in crop yield and commercial value. In Japan, the SRKN is classified into 10 races: SP1-SP5, SP6-1, SP6-2, and SP7-SP9, with the dominant race differing according to the cultivation area. Soil insecticides have previously been used to reduce the soil density of SRKNs; however, this practice is both costly and labor intensive. Therefore, the development of SRKN-resistant sweetpotato lines and cultivars is necessary. However, due to the complexity of polyploid inheritance and the highly heterogeneous genomic composition of sweetpotato, genetic information and research for this species are significantly lacking compared to those for other major diploid crop species. In this study, we utilized the recently developed genome-wide association approach, which uses multiple-dose markers to assess autopolyploid species. We performed an association analysis to investigate resistance toward SRKN-SP2, which is the major race in areas with high sweetpotato production in Japan. The segregation ratio of resistant and susceptible lines in the F-1 mapping population derived from the resistant "J-Red" and susceptible "Choshu" cultivars was fitted to 1: 3, suggesting that resistance to SP2 may be regulated by two loci present in the simplex. By aligning the double digest restriction-site associated DNA sequencing reads to the published Ipomoea trifida reference sequence, 46,982 single nucleotide polymorphisms (SNPs) were identified (sequencing depth > 200). The association study yielded its highest peak on chromosome 7 (Chr07) and second highest peak on chromosome 3 (Chr03), presenting as a single-dose in both loci. Selective DNA markers were developed to screen for resistant plants using the SNPs identified on Chr03 and Chr07. Our results showed that SRKN-SP2-resistant plants were selected with a probability of approximately 70% when combining the two selective DNA markers. This study serves as a model for the identification of genomic regions that control agricultural traits and the elucidation of their effects, and is expected to greatly advance marker-assisted breeding and association studies in polyploid crop species

Chemical Visualization of an Attractant Peptide, LURE

The pollen tube attractant peptide LUREs of Torenia fournieri are diffusible peptides that attract pollen tubes in vitro. Here, we report a method enabling the direct visualization of a LURE peptide without inhibiting its attraction activity by conjugating it with the Alexa Fluor 488 fluorescent dye. After purifying and refolding the recombinant LURE2 with a polyhistidine tag, its amino groups were targeted for conjugation with the Alexa Fluor dye. Labeling of LURE2 was confirmed by its fluorescence and mass spectrometry. In our in vitro assay using gelatin beads, Alexa Fluor 488-labeled LURE2 appeared to have the same activity as unlabeled LURE2. Using the labeled LURE2, the relationship between the spatiotemporal change of distribution and activity of LURE2 was examined. LURE2 attracted pollen tubes when embedded in gelatin beads, but hardly at all when in agarose beads. Direct visualization suggested that the significant difference between these conditions was the retention of LURE2 in the gelatin bead, which might delay diffusion of LURE2 from the bead. Direct visualization of LURE peptide may open the way to studying the spatiotemporal dynamics of LURE in pollen tube attraction

Optimization of EHL Lubrication Performance in Thrust Slide-Bearings of Scroll Compressors

Previous studies [Refs. 1, 2] revealed the formation of a uniform oil wedge at the periphery of the thrust plate, caused by the elastic deformation of the orbiting thrust plate due to the pressure difference across the orbiting thrust plate, is a significant factor in the high lubrication performance in thrust slide-bearings. In addition to the uniform wedge formation, the high oil film pressure also induces a local elastic deformation of the fixed thrust plate normal to its surface. The normal thrust plate deformation and the oil wedge effectively form an elasto-hydrodynamic-lubrication (EHL) pocket, even more effectively increasing the oil film pressure between the sliding surfaces, due to the envelopment of the oil, as confirmed in our companion paper [3], and an earlier, less-detailed contribution [4]. The present study focuses on aspects of EHL that have both positive and negative effects on the lubrication performance of the thrust slide-bearings in scroll compressors. Theoretical calculations using the average Reynolds equation and Patier-Chen solid contact theory, for the boundary of the local elastic deformation of the thrust slide-bearing, were conducted for a small cooling capacity scroll compressor driven at 3600 rpm with 0.1 kW. An approximate method was developed using characteristic curves to determine the oil film axial force, the average oil film thickness, the frictional force and the frictional coefficient. The calculations considered a variety of pressure differences due to the operation pressure and the thickness of thrust plate. Also cases with a fixed uniform wedge angle at the periphery were calculated. The calculated results suggest a possible maximum reduction in frictional coefficient of about 55% compared to that with a fixed uniform wedge angle. The reduction rate increases with decreasing thrust plate thickness, which, however, restricts the operation pressures to a lower pressure range. Design guidelines for optimizing EHL will be suggested. References: [1] Oku, T., Ishii, N., Anami, K., Knisely, C.W., Sawai, K., Morimoto, T., Hiwata, A. : Theoretical Model of Lubrication Mechanism in the Thrust Slide-Bearing of Scroll Compressors, HVAC&R Research Journal ASHRAE Vol.14, No.2, pp.239-358, 2008-3. [2] Ishii, N., Oku, T., Anami, K., Knisely, C.W., Sawai, K., Morimoto, T., Iida, N. : Experimental Study of the Lubrication Mechanism for Thrust Slide Bearings in Scroll Compressors, HVAC&R Research Journal ASHRAE Vol.14, No.2, 2008-4. [3] Ishii, N., Tsuji, T., Anami, K., Nokiyama, K., Morimoto, T., Sakuda, A., Oku, T., Sawai, K., Knisely, C.W., : “Hydrodynamic-Pressure-Induced Elastic Deformation of Thrust Slide-Bearings in Scroll Compressors and Oil Film Pressure Increase Due to Oil Envelopment,” abstract submitted to 2014 Purdue Herrick Conferences. [4] Ishii, N., Tsuji, T., Oku, T., Anami, K., Knisely, C.W., Nokiyama, K., Morimoto, T., Sakuda, A., Sawai, K. 2012 “Elasto-Hydrodynamic Lubrication Effect in Thrust-Slide Bearings of Scroll Compressors,” 2012 Purdue Conference Paper on (Paper 1438)

SnRK1 Kinase and the NAC Transcription Factor SOG1 Are Components of a Novel Signaling Pathway Mediating the Low Energy Response Triggered by ATP Depletion

Plant growth is strictly controlled by cell division, elongation, and differentiation for which adequate supplies of intracellular ATP are required. However, it is unclear how changes in the amount of intracellular ATP affect cell division and growth. To reveal the specific pathway dependent on ATP concentration, we performed analyses on the Arabidopsis mitochondria mutation sd3. The mutant is tiny, a result of a low amount of ATP caused by the disruption of Tim21, a subunit of the TIM23 protein complex localized in the inner membrane of the mitochondria. Loss of function of suppressor of gamma response 1 (SOG1) also restored the dwarf phenotype of wild type treated with antimycin A, a blocker of ATP synthesis in mitochondria. The sd3 phenotype is partially restored by the introduction of sog1, suppressor of gamma response 1, and kin10/kin11, subunits of Snf1-related kinase 1 (SnRK1). Additionally, SOG1 interacted with SnRK1, and was modified by phosphorylation in planta only after treatment with antimycin A. Transcripts of several negative regulators of the endocycle were up-regulated in the sd3 mutant, and this high expression was not observed in sd3sog1 and sd3kin11. We suggest that there is a novel regulatory mechanism for the control of plant cell cycle involving SnRK1 and SOG1, which is induced by low amounts of intracellular ATP, and controls plant development

RipsNet: a general architecture for fast and robust estimation of the persistent homology of point clouds

International audienceThe use of topological descriptors in modern machine learning applications, such as persistence diagrams (PDs) arising from Topological Data Analysis (TDA), has shown great potential in various domains. However, their practical use in applications is often hindered by two major limitations: the computational complexity required to compute such descriptors exactly, and their sensitivity to even low-level proportions of outliers. In this work, we propose to bypass these two burdens in a data-driven setting by entrusting the estimation of (vectorization of) PDs built on top of point clouds to a neural network architecture that we call RipsNet. Once trained on a given data set, RipsNet can estimate topological descriptors on test data very efficiently with generalization capacity. Furthermore, we prove that RipsNet is robust to input perturbations in terms of the 1-Wasserstein distance, a major improvement over the standard computation of PDs that only enjoys Hausdorff stability, yielding RipsNet to substantially outperform exactly-computed PDs in noisy settings. We showcase the use of RipsNet on both synthetic and real-world data. Our implementation will be made freely and publicly available as part of the open-source library Gudhi

Reproducibility and validity of food group intake in a short food frequency questionnaire for the middle-aged Japanese population

Purpose: The purpose of this study was to evaluate the reproducibility and validity of a short food frequency questionnaire (FFQ) for food group intake in Japan, the reproducibility and partial validity of which were previously confirmed for nutrients. Methods: A total of 288 middle-aged healthy volunteers from 11 different areas of Japan provided nonconsecutive 3-day weighed dietary records (DRs) at 3-month intervals over four seasons. We evaluated reproducibility based on the first (FFQ1) and second (FFQ2) questionnaires and their validity against the DRs by comparing the intake of 20 food groups. Spearman’s rank correlation coefficients (SRs) were calculated between energy-adjusted intake from the FFQs and that from the DRs. Results: The intake of 20 food groups estimated from the two FFQs was mostly equivalent. The median energy-adjusted SRs between the FFQ1 and FFQ2 were 0.61 (range 0.38–0.86) for men and 0.66 (0.45–0.84) for women. For validity, the median de-attenuated SRs between DRs and the FFQ1 were 0.51 (0.17–0.76) for men and 0.47 (0.23–0.77) for women. Compared with the DRs, the proportion of cross-classification into exact plus adjacent quintiles with the FFQ1 ranged from 58 to 86% in men and from 57 to 86% in women. According to the robust Z scores and the Bland–Altman plot graphs, the underestimation errors in the FFQ1 tended to be greater in individuals with high mean levels of consumption for meat for men and for other vegetables for both men and women. Conclusion: The FFQ demonstrated high reproducibility and reasonable validity for food group intake. This questionnaire is short and remains appropriate for identifying associations between diet and health/disease among adults in Japan